Inhibition of NADPH Oxidase-4 Potentiates 2-Deoxy-d-Glucose-Induced Suppression of Glycolysis, Migration, and Invasion in Glioblastoma Cells: Role of the Akt/HIF1α/HK-2 Signaling Axis

2015 ◽  
Vol 23 (8) ◽  
pp. 665-681 ◽  
Author(s):  
Priyanka Gupta ◽  
Kumaravelu Jagavelu ◽  
Durga Prasad Mishra
Keyword(s):  
Nadph Oxidase ◽  
Migration And Invasion ◽  
Glioblastoma Cells ◽  
Nadph Oxidase 4 ◽  
Signaling Axis

scholarly journals NADPH Oxidase 4 Regulates Inflammation in Ischemic Heart Failure: Role of Soluble Epoxide Hydrolase

2019 ◽  
Vol 31 (1) ◽  
pp. 39-58 ◽  
Author(s):  
Mark D. Stevenson ◽  
Chandrika Canugovi ◽  
Aleksandr E. Vendrov ◽  
Takayuki Hayami ◽  
Dawn E. Bowles ◽  
...  
Keyword(s):  
Heart Failure ◽  
Nadph Oxidase ◽  
Epoxide Hydrolase ◽  
Soluble Epoxide Hydrolase ◽  
Ischemic Heart ◽  
Ischemic Heart Failure ◽  
Nadph Oxidase 4

The role of cardiomyocyte Nox4D, a redox-active splice variant of NADPH oxidase-4

2018 ◽  
Vol 120 ◽  
pp. 20
Author(s):  
N. Savage ◽  
N. Anilkumar ◽  
E. Henckaerts ◽  
A.M. Shah
Keyword(s):  
Nadph Oxidase ◽  
Splice Variant ◽  
Nadph Oxidase 4 ◽  
Redox Active

scholarly journals Possible Role of NADPH Oxidase 4 in Angiotensin II-Induced Muscle Wasting in Mice

2018 ◽  
Vol 9 ◽  
Author(s):  
Tomoyasu Kadoguchi ◽  
Kazunori Shimada ◽  
Hiroshi Koide ◽  
Tetsuro Miyazaki ◽  
Tomoyuki Shiozawa ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Nadph Oxidase ◽  
Muscle Wasting ◽  
Nadph Oxidase 4

Identification of subdomains in NADPH oxidase-4 critical for the oxygen-dependent regulation of TASK-1 K+ channels

2009 ◽  
Vol 297 (4) ◽  
pp. C855-C864 ◽  
Author(s):  
Su Jung Park ◽  
Yang-Sook Chun ◽  
Kyung Sun Park ◽  
Sung Joon Kim ◽  
Si-On Choi ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Binding Domain ◽  
Ros Generation ◽  
Current Response ◽  
Cooperative Action ◽  
Sensing Mechanism ◽  
Nadph Oxidase 4 ◽  
293 Cells ◽  
Synthase Inhibitor

Hypoxic inhibition of K+ current is a critical O2-sensing mechanism. Previously, it was demonstrated that the cooperative action of TASK-1 and NADPH oxidase-4 (NOX4) mediated the O2-sensitive K+ current response. Here we addressed the O2-sensing mechanism of NOX4 in terms of TASK-1 regulation. In TASK-1 and NOX4-coexpressing human embryonic kidney 293 cells, hypoxia (5% O2) decreased the amplitude of TASK-1 current (hypoxia-Δ ITASK-1). To examine whether reactive oxygen species (ROS) mediate the hypoxia-Δ ITASK-1, we treated the cells with carbon monoxide (CO) which is known to reduce ROS generation from the heme-containing NOX4. Unexpectedly, CO failed to mimic hypoxia in TASK-1 regulation, rather blocked the hypoxia-Δ ITASK-1. Moreover, the hypoxia-Δ ITASK-1 was neither recovered by H2O2 treatment nor prevented by antioxidant such as ascorbic acid. However, the hypoxia-Δ ITASK-1 was noticeably attenuated by succinyl acetone, a heme synthase inhibitor. To further evaluate the role of heme, we constructed and expressed various NOX4 mutants, such as HBD(−) lacking the heme binding domain, NBD(−) lacking the NADPH binding domain, FBD(−) lacking the FAD binding domain, and HFBD(−) lacking both heme and FAD domains. The hypoxia-Δ ITASK-1 was significantly reduced in HBD(−)-, FBD(−)-, or HFBD(−)-expressing cells, versus wild-type NOX4-expressing cells. However, NBD(−) did not affect the TASK-1 response to hypoxia. We also found that p22 is required for the NOX4-dependent TASK-1 regulation. These results suggest that O2 binding with NOX4 per se controls TASK-1 activity. In this process, the heme moiety and FBD seem to be responsible for the NOX4 regulation of TASK-1, and p22 might support the NOX4-TASK-1 interaction.

scholarly journals Role of NADPH Oxidase-4 in Human Endothelial Progenitor Cells

2017 ◽  
Vol 8 ◽  
Author(s):  
Nora Y. Hakami ◽  
Amaresh K. Ranjan ◽  
Anandwardhan A. Hardikar ◽  
Greg J. Dusting ◽  
Hitesh M. Peshavariya
Keyword(s):  
Nadph Oxidase ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Endothelial Progenitor ◽  
Nadph Oxidase 4

scholarly journals Regulation of cellular oxidative stress and apoptosis by G protein-coupled receptor kinase-2; The role of NADPH oxidase 4

2016 ◽  
Vol 28 (3) ◽  
pp. 190-203 ◽  
Author(s):  
Tiju Theccanat ◽  
Jennifer L. Philip ◽  
Abdur M. Razzaque ◽  
Nicholas Ludmer ◽  
Jinju Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nadph Oxidase ◽  
G Protein ◽  
Receptor Kinase ◽  
G Protein Coupled Receptor ◽  
Nadph Oxidase 4 ◽  
G Protein Coupled

scholarly journals HOXA10 mediates epithelial-mesenchymal transition to promote gastric cancer metastasis partly via modulation of TGFB2/Smad/METTL3 signaling axis

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Chenlong Song ◽  
Chongzhi Zhou
Keyword(s):  
Gastric Cancer ◽  
Western Blot ◽  
Lung Metastasis ◽  
Essential Role ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Signaling Axis

Abstract Background Homeobox A10 (HOXA10) belongs to the HOX gene family, which plays an essential role in embryonic development and tumor progression. We previously demonstrated that HOXA10 was significantly upregulated in gastric cancer (GC) and promoted GC cell proliferation. This study was designed to investigate the role of HOXA10 in GC metastasis and explore the underlying mechanism. Methods Immunohistochemistry (IHC) was used to evaluate the expression of HOXA10 in GC. In vitro cell migration and invasion assays as well as in vivo mice metastatic models were utilized to investigate the effects of HOXA10 on GC metastasis. GSEA, western blot, qRT-PCR and confocal immunofluorescence experiments preliminarily analyzed the relationship between HOXA10 and EMT. ChIP-qPCR, dual-luciferase reporter (DLR), co-immunoprecipitation (CoIP), colorimetric m6A assay and mice lung metastasis rescue models were performed to explore the mechanism by which HOXA10 accelerated the EMT process in GC. Results In this study, we demonstrated HOXA10 was upregulated in GC patients and the difference was even more pronounced in patients with lymph node metastasis (LNM) than without. Functionally, HOXA10 promoted migration and invasion of GC cells in vitro and accelerated lung metastasis in vivo. EMT was an important mechanism responsible for HOXA10-involved metastasis. Mechanistically, we revealed HOXA10 enriched in the TGFB2 promoter region, promoted transcription, increased secretion, thus triggered the activation of TGFβ/Smad signaling with subsequent enhancement of Smad2/3 nuclear expression. Moreover, HOXA10 upregulation elevated m6A level and METTL3 expression in GC cells possible by regulating the TGFB2/Smad pathway. CoIP and ChIP-qPCR experiments demonstrated that Smad proteins played an important role in mediating METTL3 expression. Furthermore, we found HOXA10 and METTL3 were clinically relevant, and METTL3 was responsible for the HOXA10-mediated EMT process by performing rescue experiments with western blot and in vivo mice lung metastatic models. Conclusions Our findings indicated the essential role of the HOXA10/TGFB2/Smad/METTL3 signaling axis in GC progression and metastasis.

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